Efficacy and safety of TOBI Podhaler® in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study.
The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa (Pa) sputum density in patients with bronchiectasis (BE).This is a phase II, double-blind, randomised study in BE patients aged ≥18 years with chronic Pa infection. Patients were randomised 1:1:1 to either Cohort A: 3 capsules of TIP O.D. (84 mg); Cohort B: 5 capsules O.D. (140 mg) or Cohort C: 4 capsules B.I.D. (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively, and were followed up for 8 weeks.Overall, 107 patients were randomised to Cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the Pa sputum density from baseline to Day 29 versus placebo in a dose-dependent manner (p≤0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous-TIP and 42.9% on cyclical-TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of BE was the most frequent (37.4%) adverse event (AE). Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to AEs.Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the Pa sputum density in patients with BE and chronic Pa infection.